An enzyme material called hyaluronidase has been known for a number of years, this material catalysing the hydrolysis of hyaluronic acid, the cement substance of tissues.
Many of the hyaluronidase preparations previously available have contained very large amounts of other enzymatically-active materials, in addition to the enzyme which is thought to be actually responsible for the catalysis of the hydrolysis of hyaluronic acid. The heterogeneous nature of hyaluronidase is discussed in a paper by Greiling et al. (Z.physiol.Chem., 340, 243/1965).
Several processes are known for the purification of hyaluronidase (see our British Patent Specifications Nos. 1,060,513 and 1,425,918) and this purified material has been successfully used for the treatment of myocardial infarct and of peripheral circulatory disturbances, including those associated with gangrene.
This extremely useful action of hyaluronidase appears to be due to its "spreading" ability, i.e. its ability to promote rapid diffusion of injected fluids through tissues, as well as its ability to break down aggregations which are responsible for or contribute to the genesis of infarcts and circulatory disturbances. Previously known hyaluronidase preparations were also observed to have a permeability-increasing activity which manifested itself by increasing capillary permeability; we have also observed that known crude hyaluronidase preparations bring about a reduction of the blood pressure. However, such activities are undesirable when hyaluronidase is used to treat myocardial infarcts and peripheral circulatory disturbances.
It has recently been found by Houck and Chang (Inflammation, 3(4), 447-451/1979) that hyaluronidase preparations contain a component which increases the permeability of the microcirculation in skin.
It is an object of the present invention to provide an enzyme preparation which can be obtained from hyaluronidase but which has a greatly reduced content of the component which increases permeability and which also does not bring about a reduction of the blood pressure.